The NIH sponsored Diabetes Control and Complications Trial (DCCT study) clearly demonstrates that light blood glucose control dramatically slows down the onset of the devastating complications of diabetes. However, lightening glucose control is both difficult and potentially hazardous. Hypoglycemia occurs 2-3 times more often when using intensive insulin management. Half of these episodes occur during sleep. A third of daytime episodes occur without warning. Clearly a means of tracking glucose continuously with trend displays and alarm functions is needed to reduce this risk while facilitating tighter control of blood glucose. Phase l proposes taking a subcutaneously implantable glucose sensor that has already been tested through three months in a dog model, and improving reliability for eventual human trials. Specifically, we propose to stabilize capillary blood supply at the inside of the sensors foreign body capsule by using a promising new approach based on material microarchitecture stimulation of chronic granuloma tissue. In additional efforts to improve sensor reliability , we will quantify in vivo membrane enzyme decay rates and use this information for better sensor lifetime prediction and for subsequent improvements in membrane formulation. Upon completion of this Phase l research, an application will be made to the Human Subjects Committee of the University of Wisconsin Medical School seeking permission for short-term human clinical trials of this sensor during Phase 11 of this proposal. PROPOSED COMMERCIAL APPLICATION: Only cardiovascular disease and cancer cause more death than diabetes. Diabetes is the leading cause of blindness, limb amputation, and kidney failure. If successful, this glucose sensor research opens the possibility of diabetic patients monitoring their tissue glucose concentration as easily as reading a watch. With additional engineering, a successful sensor could control implanted insulin pumps currently under development in other research laboratories to provide an artificial pancreas for the millions of patients with this debilitating disease.